Clinical Trials Register

Summary
EudraCT Number:	2015-003350-41
Sponsor's Protocol Code Number:	APOCT-003
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2018-05-29
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Denmark - DHMA

A.2

EudraCT number

2015-003350-41

A.3

Full title of the trial

The Diabetes Virus Detection and Intervention Trial (DiViDIntervention)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Treatment against viruses at the onset of type 1 diabetes

A.4.1

Sponsor's protocol code number

APOCT-003

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Division pf Paediatric and Adolescent Medicine, Oslo University Hospital
B.1.3.4	Country	Norway
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Oslo University Hospital
B.4.2	Country	Norway
B.4.1	Name of organisation providing support	Apodemus AB
B.4.2	Country	Sweden
B.4.1	Name of organisation providing support	Innodia
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Division of Paediatric and Adolescent Medicine, Oslo University Hospital
B.5.2	Functional name of contact point	Knut Dahl-Jorgensen
B.5.3	Address:
B.5.3.1	Street Address	P.O. Box 4956 Nydalen
B.5.3.2	Town/ city	Oslo
B.5.3.3	Post code	0424
B.5.3.4	Country	Norway
B.5.4	Telephone number	+4792233550
B.5.5	Fax number	+4722118663
B.5.6	E-mail	knut.dahl-jorgensen@medisin.uio.no

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Pleconaril
D.3.4	Pharmaceutical form	Oral liquid
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PLECONARIL
D.3.9.1	CAS number	153168-05-9
D.3.9.2	Current sponsor code	Pleconaril
D.3.9.4	EV Substance Code	SUB09957MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Ribavirin
D.3.4	Pharmaceutical form	Oral liquid
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Ribavirin
D.3.9.1	CAS number	36791-04-5
D.3.9.3	Other descriptive name	RIBAVIRIN
D.3.9.4	EV Substance Code	SUB10297MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Oral liquid
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Oral liquid
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Newly diagnosed Type 1 Diabetes diagnosed within the previous three weeks at time of screening. Female and male patients between the ages of 6 and 15 years will be recruited.

E.1.1.1

Medical condition in easily understood language

In type 1 diabetes, the insulin secretion from the pancreas is insufficient to maintanin a normal blood glucose. The disease leads to increased morbidity and mortality an the causes remains unknown.

E.1.1.2

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10067584
E.1.2	Term	Type 1 diabetes mellitus
E.1.2	System Organ Class	10027433 - Metabolism and nutrition disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The main study objective is to describe the influence of antiviral treatment (Pleconaril +Ribavirin) versus placebo on progression of disease and residual insulin secretion in patients newly-diagnosed with type 1 diabetes at the age 6 -15 years. The study design a double-blind, placebo controlled, prospective, randomized trial examining the effect of antiviral treatment given for 6months on residual insulin secretion.

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

All of the following conditions must apply to the prospective patient at screening prior to receiving study agent:
1. Diagnosed type 1 Diabetes (E10.9). First injection of insulin maximum three weeks prior to inclusion.
2. Must be willing and capable of taking the study drugs and meet for tests and follow up as described.
3. Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to ICH GCP, and national/local regulations.
4. Aged 6.00-15.99 years at inclusion.

E.4

Principal exclusion criteria

Patients will be excluded from taking part in the study if they meet any of the following criteria:
1. Treatment with any oral or injected anti-diabetic medications other than insulin.
2. A history of haemolytic anaemia or significantly abnormal haematology results at screening.
3. History of severe cardiac disease previous six months
4. Impaired renal function
5. Participation in other clinical trials with a new chemical entity within the previous 3 months.
4. Inability or unwillingness to comply with the provisions of this protocol
5. Females who are lactating or pregnant.
6. Males or females (after menarche) not willing to use highly effective contraception (progesterone-only hormonal anticonception with inhibition of ovuulation or sexual abstinence) and anti-barrier contraception (condoms), if sexually active, during the treatment period and in the following 7 months
7. Presence of serious disease or condition, which in the opinion of the investigator makes the patient non-eligible for the study.

E.5 End points

E.5.1

Primary end point(s)

Change in mean residual insulin secretion in the ITT-population measured by Mixed Meal Tolerance Test (MMTT) stimulated C-peptide two-hour area under the curve profile from visit 1 to 12 months after initiation of study treatment.

E.5.1.1

Timepoint(s) of evaluation of this end point

12 months after inclusion in the study and initiation of study treatment.

E.5.2

Secondary end point(s)

The secondary end points are:
1. Change in mean residual insulin secretion measured by stimulated C-peptide two-hour area under the curve profile visit 1 to 3 months, 6 months, 24 months and 36 months
2. Proportion of patients with peak residual insulin secretion measured by MMTT: stimulated C-peptide >0,2 pmol/L.
3. Fasting and meal stimulated C-peptide from blood sampled on filter paper at home at 4 weekly intervals throughout the study period
4. Mean Insulin dosage per kilo bodyweight for 24 hours one week before each control
5. HbA1c at every Control. Both the absolute level and the change from visit 1 will be analysed.
6. Number of severe hypoglycemic events
7. Insulin-dose-adjusted HbA1c (IDAA1c)
8. Proinsulin/c-peptide ratio in serum as a measure of beta cell stress
9. Change in presence of Enterovirus (PCR and neutaralizing antibodies) in nose, blood and stool

E.5.2.1

Timepoint(s) of evaluation of this end point

3 months, 6 months, 24 months and 36 months after inclusion in the study and initiation of study treatment.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Add on to insulin treatment

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Continuation of treatment will not be provided

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2018-09-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-09-26

P. End of Trial
P.	End of Trial Status	Ongoing

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